Chitosan‐Based Heparan Sulfate Mimetics Promote Epidermal Formation in a Human Organotypic Skin Model

Biomimetic materials that replicate biological functions have great promise for use as therapeutics in regenerative medicine applications. Heparan sulfate (HS) is the natural binding partner for growth factors enabling longer half‐lives and potentiation of their signaling. In this study a water soluble chitosan‐arginine is modified with sulfate moieties in order to mimic the structure of HS. Sulfated chitosan‐arginine with a degree of sulfation of 58% binds fibroblast growth factor 2 with higher affinity than HS. The sulfated chitosan‐arginine also promotes epithelial cell migration and supports the formation of an expanded epidermis in an organotypic skin model. Furthermore, sulfated chitosan‐arginine promotes the expression of the HS proteoglycan, perlecan, by both epithelial and fibroblast cells. Perlecan itself modulates the activity of mitogens and is essential for the formation of the epidermis. The synthesized sulfated Ch‐Arg derivatives mimic HS, support formation of the epidermis, and thus have the potential to assist in wound healing. Modification of chitosan‐arginine to incorporate sulfate groups mimics heparan sulfate, a binding partner of growth factors. By altering the degree of sulfate modification this biomimetic material has the potential to assist in wound healing through the binding of growth factors, promotion of epithelial cell migration, and epidermis formation.